rs1802059
badMag 3.8This is a synonymous variant in the MTRR gene — it does not change the protein's amino acid sequence.
Key Literature Trait Associations
Congenital heart disease
The MTRR A66G G allele is associated with modestly increased risk of congenital heart disease (CHD), with a pooled OR of 1.35 (95% CI 1.14–1.59) for the G allele in a meta-analysis of nine studies (914 cases, 964 controls, 441 families). The association appears stronger in Asian populations (GG vs AA: OR 1.43). A subsequent meta-analysis of eight studies (3,592 cases, 3,638 controls) confirmed elevated risk (GG vs AA: OR 1.33; 95% CI 1.02–1.74). Two recent Chinese case-control studies further supported large homozygous effects (AA vs GG ORs of 3.95–5.13), with maternal folic acid supplementation significantly mitigating offspring risk.
Methionine Synthase Reductase Activity
The MTRR A664A variant (rs1802059) is a synonymous polymorphism in methionine synthase reductase. The A allele does not change the amino acid sequence. This variant is part of the MTRR haplotype block and has limited independent evidence for functional impact on B12 recycling or homocysteine metabolism.
Down syndrome
Maternal MTRR A66G G allele carriage has been associated with marginally increased risk of having a child with Down syndrome (trisomy 21), hypothesized to occur through impaired one-carbon metabolism leading to abnormal methylation of pericentromeric DNA and chromosomal nondisjunction. A meta-analysis of 15 case-control studies found overall OR 1.22 (95% CI 1.02–1.46), representing marginal significance. However, an earlier meta-analysis of 11 studies found no significant association, and evidence remains inconsistent across ethnicities. The biological plausibility is supported by the role of MTRR in maintaining methylation homeostasis, but the clinical magnitude is small.
Neural tube defects
The maternal MTRR A66G G allele shows a borderline association with neural tube defect (NTD) risk in offspring, with a meta-analysis pooled OR of 1.21 (95% CI 0.98–1.49) for the G allele — statistically marginal overall. A large Irish case-control study (447 mothers, 476 controls) found no significant maternal association (OR 1.14, p=0.16) but did identify a dominant paternal G-allele effect (OR 1.46, p=0.019). Evidence is inconsistent across populations and the effect appears much weaker than for MTHFR C677T, with folate fortification likely attenuating any genetic contribution.
Colorectal cancer
A meta-analysis of 13 studies (5,511 cases, 7,265 controls) found the MTRR 66G allele associated with a modest increase in colorectal cancer risk overall (OR 1.11, 95% CI 1.01–1.18), with the strongest signal in Caucasian populations (GG vs AA: OR 1.18, 95% CI 1.03–1.36). The proposed mechanism involves impaired methionine synthase activity leading to uracil misincorporation into DNA and aberrant methylation patterns in colorectal tissue. The overall effect size is small, and the authors noted that further confirmatory studies were needed.
Acute lymphoblastic leukemia
A meta-analysis of studies encompassing 2,913 leukemia cases and 4,764 controls found no significant overall association between MTRR A66G and leukemia risk, but revealed population-stratified effects: in Caucasians and children, the GG genotype was associated with decreased ALL risk, while in Asian populations an increased risk was observed. The direction of effect thus varies by ancestry, and the overall null result means clinical applicability is limited. The proposed mechanism involves folate pathway effects on thymidylate synthesis and DNA methylation during lymphocyte development.
▶ClinVar annotation
Disorders of Intracellular Cobalamin Metabolism; Methylcobalamin deficiency type cblE (HMAE); not specified
View on ClinVar →▶Research that mentions this SNP (2)
▶Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern ChinaAssociationN=321Yulian Fang et al.(2018)· Child's Nervous System
A case-control study of 152 NTD patients and 169 controls in Han Chinese population identified three folate metabolism pathway SNPs associated with neural tube defects: rs2236225 in MTHFD1 (allele A, OR=1.500; AA genotype OR=2.862), rs1801133 in MTHFR (allele T, OR=1.552; TT genotype OR=2.344), and rs1801394 in MTRR (allele G, OR=1.533; GG genotype OR=2.355). The study demonstrates genetic variation in folate metabolism significantly affects NTD susceptibility.
▶Genetic variation at the CELF1 (CUGBP, elav‐like family member 1 gene) locus is genome‐wide associated with Alzheimer's disease and obesityReviewAnke Hinney et al.(2014)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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